We propose that periodontal disease is a chronic inflammation induced and maintained by the persistence in tissue of slowly degradable material which has a direct toxic effect on tissue. Bacterial cell walls, which have these properties of persistence and toxicity, will be isolated from representative bacteria in the human gingival crevice. We will induce experimental disease by injection of cell wall fragments into the gingival tissue of inbred strains of rats. This model will be used to study mechanisms by which bacterial cell wall structures induce chronic inflammatory disease. The influence of age, sex, cellular and humoral immune responses will be studied. Susceptible and resistant inbred strains of rats will be utilized to investigate genetic control of these factors as determinants of the experimental disease. The relevance of this experimental model to human periodontal disease will be tested by comparing in vitro responses of peripheral lymphocytes from patient and control groups to selected bacterial cell wall antigens. Evidence for localization of persistent cell wall antigens in periodontal tissue of patients will also be sought.